chr3-79519823-A-G

Position:

• chr3-79519823-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002941.4(ROBO1):​c.88+70001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 151,488 control chromosomes in the GnomAD database, including 41,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (41348 hom., cov: 28)
• Consequence: ROBO1 NM_002941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

Genes affected

ROBO1 (HGNC:10249): (roundabout guidance receptor 1) Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The product of this gene is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. A related gene is located at an adjacent region on chromosome 3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO1	NM_002941.4	c.88+70001T>C		intron_variant		ENST00000464233.6	NP_002932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO1	ENST00000464233.6	c.88+70001T>C		intron_variant		5	NM_002941.4	ENSP00000420321.1
ROBO1	ENST00000492990.1	n.*210+6669T>C		intron_variant		3		ENSP00000419915.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110247 AN: 151370 Hom.: 41282 Cov.: 28

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.691

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.729 AC: 110378 AN: 151488 Hom.: 41348 Cov.: 28 AF XY: 0.724 AC XY: 53559 AN XY: 73980

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.694

Alfa AF: 0.699 Hom.: 4731

Bravo AF: 0.737

Asia WGS AF: 0.627 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7623809; hg19: chr3-79568973;